ARUP's Laboratory Test Directory

Fragile X (FMR1) Diagnostic : 0040011
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Patient History For Molecular Genetic Testing
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Additional Technical Information


Mnemonic: FRAG X

Ordering Recommendation: Use to diagnose fragile X syndrome in individuals with characteristic clinical symptoms or a positive family history. Fragile X (FMR1) Screen with Reflex to Fragile X (FMR1) Diagnostic (2001946) may be considered in the absence of a family history or to determine carrier status.
Methodology: Southern Blot/Polymerase Chain Reaction/Fragment Analysis
Performed: Sun-Sat
Reported: 4-14 days
Specimen Required: Collect: Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation: Transport 5 mL whole blood. (Min: 1.5 mL)

Storage/Transport Temperature: Room temperature. If transport time will exceed 48 hours: Refrigerated.

Stability (collection to initiation of testing): Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Reference Interval:
By report
Interpretive Data: Fragile X (FMR1) Diagnostic
Characteristics: Fragile X syndrome, the most common heritable form of mental retardation, is characterized by moderate mental retardation in males and mild mental retardation in females, hyperactivity, perseverative speech, social anxiety, poor eye contact, hand flapping or biting, autism spectrum disorders behavioral phenotype, and connective tissue anomalies. Adult males may have physical findings including: macroorchidism, a long narrow face, prominent ears and jaw, and a single palmar crease.
Incidence: 1 in 4,000 Caucasian males and 1 in 8,000 Caucasian females; unknown in other ethnicities
Inheritance: X-linked dominant.
Penetrance: Reduced in females.
Cause: Expansion of the FMR1 gene CGG triplet repeat.
Full mutation: >200-230 CGG repeats (methylated)
Premutation: 55-200 CGG repeats (unmethylated)
Intermediate: 45-54 CGG repeats (unmethylated)
Normal: 5-44 CGG repeats (unmethylated)
Clinical Sensitivity: 99 percent.
Methodology: PCR and Southern blot hybridization. Methylation analysis is performed to distinguish between premutation and full mutation alleles. The sex chromosome gene amelogenin is used to confirm gender but also may indicate the possibility of X chromosome aneuploidies such as Klinefelter or Turner syndrome.
Analytic Sensitivity and Specificity: 99 percent
Limitations: Analytic sensitivity may be compromised by PCR primer site mutations.



Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS
 
Phenotype Number of CGG Repeats
Unaffected < 45
Intermediate 45-54
Premutation 55-200
Affected >200

CPT Code(s): 81244
Cross References: Inherited Mental Retardation (Fragile X (FMR1) Diagnostic) , Martin-Bell Syndrome (Fragile X (FMR1) Diagnostic)